Previous research has indicated that selected strains can be used as a tool for the study of the neural mechanisms responsible for reward comparison processes. In particular, Lewis rats have a greater avidity for drugs of abuse which serves to override responsiveness for natural rewards, while the drug non-preferring Fischer rats ramain impervious to these reward comparison processes. Thus, we hypothesize that the differences in the molecular characteristics between Lewis and Fischer rats mediate the difference in responding for a saccharin CS following taste-drug pairings. The proposed studies will test this hypothesis by employing behavioral, lesion, and molecular techniques to examine the generality of the phenomenon (Specific Aim I), the nature of the difference in responding between the Lewis and Fischer rats (Specific Aim II), and the role of specific neural substrates in mediating this difference (Specific Aim III).